We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.

Qualitative methodology provides new insights and richness of data regarding adults receiving home PN. The positive description of QOL in this study contrasts with the published nutrition literature. It is important for healthcare practitioners to understand and discuss the realities of home PN and lifestyle adaptation.

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The study of sexual exploitation of trafficked victims cannot be done without understanding their enforced isolation. To better understand the dynamics of isolation, this study examined how traffickers used different elements of isolation and how such tactics may have contributed to the traffickers’ success in maintaining control over the victim(s). We examined in-depth narratives from 14 women between the ages of 20 to 53, primarily immigrants, who were recruited from an agency serving victims of sex trafficking in a large metropolitan city. The tactics used by traffickers varied and included not only the commonly defined structural isolation in which victims are restricted physically and socially, but also included a shrinking of safe social space and an elimination of privacy and social support. The latter, which we label as functional isolation, refers to instances when survivors are surrounded by peers who are either unreliable or aligned with the trafficker and thus are unable to give true social support. Survivors reported a combination of isolation tactics (i.e., both structural isolation and functional isolation). The different interwoven types and patterns of isolation reported by former victims of trafficking help address a dearth in the coercive control and abuse literature, providing a richer understanding of isolation in trafficking survivors.

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